Recent trends to prolong life and expedite hospital discharge of cancer patients have meant that family members are assuming increased responsibility for the care of relatives suffering from cancer. Although the literature has begun to recognize the important role of family members and the potential stress that these individuals experience during care provision, many studies are characterized by small sample sizes, a lack of conceptual clarity, and short-term research designs. The proposed study aims to address these shortcomings by developing a comprehensive longitudinal protocol that explores sociodemographic context, stress, resources, caregiver-care recipient communication, and global outcomes (e.g., psychological well-being, physical health) of 200 family caregivers of cancer patients recruited from the Radiation Medicine Clinic at the University of Kentucky. Moreover, the proposed study will test and refine a series of hypotheses that will provide empirical support for a comprehensive model of caregiver stress and coping through intensive longitudinal analyses (e.g., growth curve modeling). A parallel and longitudinal qualitative component of this study will include information collected from semi-structured interviews of a subsample of family members (n = 20) that will provide narrative information on the lived experience of cancer care giving. The proposed study will merge the intensive quantitative and qualitative data available to refine the stress process model for cancer care giving. We anticipate this multi-method analysis will expand understanding of the stress process among family caregivers and their relatives suffering from cancer, refine the development and targeting of psychosocial interventions for care-giving families, and serve as the basis for a multi-year, R01-level study of the cancer care-giving career.